Atopic dermatitis (AD) is a paradigmatic skin disease in which multiple gene-gene and gene-environment interactions play a pivotal role. Although the complex pathophysiologic network of AD explains the large spectrum of risk and trigger factors, it is far from being comprehensively understood. Hence, genetic modifications underlying the dysfunction of the epidermal skin barrier as well as the close interaction of innate and adaptive immune mechanisms were the focus of intensive research studies. This review aims to summarize the most recent findings in this field.